1. Field of Invention
This invention relates to oxidized polysaccharide materials suitable for medical and surgical applications. In particular, the invention describes periodate oxidized microbial cellulose that is produced to have a specific mechanical and degradation profile, depending on the desired application of the oxidized cellulose.
The invention also relates to the use of the periodate oxidized microbial cellulose as a bioresorbable matrix for human tissue substitutes, closure reinforcement, suture buttressing, guided tissue regeneration, musculoskeletal applications, active agent delivery and tissue engineering scaffolds.
2. Background of the Invention
Oxidized cellulose has long been manufactured for use medically as haemostatic agents (e.g., SURGICEL™, Ethicon, Somerville, N.J. and Oxycell™, Becton-Dickinson, Morris Plains, N.J.) and as a barrier material to prevent adhesions following surgery (e.g., INTERCEED™, Ethicon, Somerville, N.J.). The key feature of oxidized cellulose is that it is absorbable when implanted in the body, whereas non-oxidized cellulose is not. The proposed mechanism of resorption of oxidized cellulose is by hydrolytic cleavage of the polymer into smaller oligosaccharides which are further metabolized and eliminated by the body. Complete absorption of such materials can be substantially achieved in two weeks to three months after implantation.
Most oxidized cellulose that is commercially available is plant-derived or synthetically regenerated to fabricate the resulting medical device. The material is first processed to the desired physical form and is then woven or knitted into a fabric prior to exposure to an oxidizing agent. Dinitrogen tetroxide is believed to be the only oxidizing agent currently being used to produce oxidized cellulose medical products. The use of other oxidation agents has been suggested, however, but to date, there have been no reports of commercially available oxidized cellulose medical devices created by other means besides the dinitrogen tetroxide oxidation process. Thus, the vast majority of clinical data on oxidized cellulose comprises non-microbial forms of cellulose oxidized by dinitrogen tetroxide.
Although other oxidation procedures have been developed to create bioresorbable cellulose, such processes do not describe using cellulose from microbial sources. For example, Kumar (U.S. Pat. No. 6,800,753) discloses sodium meta-periodate as an oxidizing agent for regenerated cellulose. Furthermore, Singh discloses the use of sodium meta-periodate for oxidation of cellulose, but only describes a powdered form of cellulose from a non-microbial source.
Combining Kumar and Singh, it is not evident that the use of microbial cellulose as a starting material for periodate oxidized cellulose would result in a mechanically functional material. In fact, Kumar specifically discourages the use of cellulose from microbial sources because of the lack of plasticity of microbial cellulose and the loss of the higher ordered structure of microbial cellulose during the solvent dissolving step. And it is not apparent from Singh that microbial cellulose would be suitable because of the crystalline and laminar structure of microbial cellulose. In fact, the current inventors were unexpectedly able to oxidize microbial cellulose and maintain mechanical strength while producing a biodegradable material.
In addition, neither Kumar nor Singh describe the use of supporting electrolytes during the periodate oxidation process or the utilization of differing drying techniques to confer different mechanical and degradation properties on the oxidized cellulose. Likewise, Jaschinski et al. (U.S. Pat. No. 6,635,755) describe a polysaccharide oxidation process with periodate in conjunction with TEMPO to create a material with oxidation occurring at all three alcoholic sites of the anhydroglucose repeat unit. Jaschinski et al., however, does not describe microbial cellulose as a suitable polysaccharide material and do not rely on the specific oxidative nature of periodate in conjunction with a supporting electrolyte.
Furthermore, Kim et al. describe periodate oxidation of plant cellulose obtained from marine alga. The oxidation process consists of the oxidation of cellulose microfibrils at a ratio of 10.7 mol NaIO4 for 1 mol of glucopyranose for the desired reaction time. Again there is no description of the use of a supporting electrolyte during the oxidation process or a specific drying technique. Kim concludes that it is very important to choose the proper starting material to control the oxidation process, thus demonstrating that not all cellulose reacts the same when oxidized with periodate.
Ring et al. (U.S. Pat. Nos. 4,588,400, 4,655,758, and 4,788,146), however, does disclose the use of microbial cellulose for topical medical applications but does not describe oxidizing such films to produce a bioresorbable oxidized microbial cellulose for use as implantable medical devices or tissue engineering matrices. And Hutchens et al. (U.S. Patent Application No. 20040096509) also describe microbial cellulose but do not teach a bioresorbable version of the cellulose.
There is a need in the art for oxidized microbial cellulose that can have a given mechanical and degradation profile to fit a number of medical and surgical applications. Indeed, the use of microbial cellulose allows the creation of oxidized cellulose films which are able to maintain a high degree of laminar structure and crystallinity as opposed to amorphous oxidized regenerated cellulose. The non-woven laminar structure of microbial cellulose allows the material to maintain mechanical strength and at the same time be rendered bioresorbable.